Renal transplantation in patients older than 60 years has long been regarded with skepticism owing to the increased risk of complications although, as compared with dialysis treatment, a graft seems to improve not only the quality of life but also long-term patient survival. This study sought to analyze the impact of recipient age older than 60 years on patient and graft outcomes.

BACKGROUND: The objective of this study was to evaluate differences in outcomes of allograft nephrectomies performed by extracapsular versus intracapsular techniques. METHODS: From 1993 to 2010, we performed 89 allograft nephrectomies, including 57 by extracapsular techniques and 32 by intracapsular, chosen according to feasibility at the beginning of the surgery. Fisher exact test and logistic regression were used for statistical analysis. Survival estimates after allograft nephrectomy were calculated according to the Kaplan-Meier method. RESULTS: After a mean graft survival of 49.7 months, the indications for transplant nephrectomy were chronic rejection (39.3%), acute rejection (22.5%), infection/sepsis (19.1%), gross hematuria (6.7%), renal vein thrombosis (6.7%), renal artery thrombosis (3.4%), and graft rupture (2.3%). Mean operative time, blood loss, transfusions, and complications were similar between the extracapsular and intracapsular groups. The only difference in surgical aspects between the 2 groups was the mean hospital stay, which was longer for the extracapsular group (13.8 vs 7.6 days; P = .01), a result that was confirmed by multivariate analysis (odds ratio, 1.05; 95% confidence interval, 1.0-1.1; P = .03). CONCLUSIONS: Our experience showed no significant advantages in favor of the intracapsular technique except for a shorter length of hospital stay than after the extracapsular procedure

PURPOSE: Patients with end-stage renal disease (ESRD) have an increased risk of developing renal cell carcinoma (RCC). This retrospective study compared clinical and pathological outcomes of RCC occurring in native kidneys of patients with ESRD (whether they underwent kidney transplantation or not) with those of renal tumors diagnosed in the general population. METHODS: The study included a total of 533 patients with RCC. The ESRD cohort included 92 patients with RCC in native kidneys. Of these, 58 and 34 cases were identified before (pre-Tx group) and after kidney transplantation (post-Tx group), respectively. The control group was composed of 441 RCCs diagnosed in the general population. Variables were compared by chi-square and Student's t tests. Cancer-specific survival was assessed by Kaplan-Meier and Cox methods. RESULTS: The ESRD groups had smaller (P = 0.001), lower-grade, and lower-stage tumors than the non-ESRD group (P = 0.001). The papillary RCC rate was higher in the ESRD groups (P = 0.01). Ten-year cancer-specific survivals were 94.5, 87.9, and 74.6 % in pre-Tx, post-Tx, and non-ESRD patients, respectively (P = 0.003). Mean follow-up was 90.2 months. At multivariate analysis, tumor size (HR = 1.10), pathological stage (HR = 1.46), presence of nodal (HR = 2.22) and visceral metastases (HR = 3.49), and Fuhrman grade (HR = 1.48) were independent adverse prognostic factors for cancer-specific survival. CONCLUSIONS: Native kidney RCCs arising in ESRD patients are lower stage and lower grade as compared to RCCs diagnosed in the general population, and these tumors exhibit favorable clinical and outcome features.

PURPOSE: In clear cell renal cell carcinoma tissue samples we identified and characterized a population of renal cell carcinoma derived CD133+/CD24+ cancer cells. We studied differences between these cells and their nonneoplastic counterpart, tubular adult renal progenitor cells. MATERIALS AND METHODS: CD133+/CD24+ renal cell carcinoma derived cells were isolated from 40 patients. The mesenchymal phenotype and stemness proteomic profile of these renal cell carcinoma derived cells were characterized. Colony forming efficiency and self-renewal ability were tested by limiting dilution. Tumorigenic properties were evaluated in vitro by soft agar assay. The angiogenic response was evaluated in vivo by the chorioallantoic membrane angiogenic assay. Microarray analysis was performed on 6 tubular adult renal progenitor cell and 6 renal cell carcinoma derived cell clones. Membrane protein expression was evaluated by flow cytometry and immunofluorescence staining. RESULTS: CD133+/CD24+ cells were isolated from normal and tumor kidney tissue. Fluorescence activated cell sorting revealed that renal cell carcinoma derived cells did not express mesenchymal stem cell markers. CD133+/CD24+ tumor cells were more undifferentiated than tubular adult renal progenitor cells. Renal cell carcinoma derived cells were clonigenic and could differentiate into adipocytes, epithelial and osteogenic cells. They could also regenerate tumor cells in vitro and induce angiogenesis in vivo. Gene expression profile identified CTR2 as a membrane marker for this neoplastic population. CTR2 was involved in renal cell carcinoma derived cell cisplatin resistance. CONCLUSIONS: Our results indicate the presence of a CD133+/CD24+/CTR2+ cancer cell population in clear cell renal cell carcinoma. These cells have some stem cell-like features, including in vitro self-maintenance and differentiating capabilities, and they can induce an angiogenic response in vivo.

CA 15-3, CA 125 and β-2 microglobulin are three common tumor markers currently used for diagnosis, prognosis, assessment of therapeutic response, and/or to evaluate recurrence in breast and ovarian cancer and malignant lymphoproliferative disorders, respectively. In the present prospective study we assessed the role of these three serum proteins as biomarkers for renal cell carcinoma (RCC), as well as any association between tumor marker levels and clinical-pathological parameters. CA 15-3, CA 125, and β-2 microglobulin were preoperatively measured in 332 patients who underwent nephrectomy for RCC. Estimates of cancer-specific survival (CSS) was calculated according to the Kaplan-Meier method. Multivariate analysis was performed to identify the most significant variables for predicting CSS. Preoperatively, 35.2% (n = 117), 9.6% (n = 32) and 30.4% (n = 101) of the patients had abnormal levels of CA 15-3, CA 125 and β-2 microglobulin, respectively. Statistically significant differences resulted between CA 15-3, CA 125 and β-2 microglobulin values and tumor size, Fuhrman grade, presence of lymph node, and visceral metastases. CSS was significantly decreased for patients with high levels of CA 15-3, CA 125, and β-2 microglobulin (P < 0.0001, P < 0.0001, and P = 0.001, resp.). At multivariate analysis only age, the presence of visceral metastases, and high levels of CA 15-3 were independent adverse prognostic factors for CSS.

INTRODUCTION: Ischemia-reperfusion injury (IRI) causes a high rate of delayed graft function (DGF), the most frequent complication in the immediate postoperative period after cadaveric donor kidney transplantation. Herein we evaluated the impact of donor and recipient characteristics on DGF development in terms of the incidence of acute rejection episodes, hospital stay, renal function, and long-term graft and patient survivals. MATERIALS AND METHODS: Between February 1998 and July 2011, 761 patients underwent cadaveric donor kidney transplantations. DGF was defined as the need for dialysis in the first week. Patients were subdivided according to initial graft function as immediate graft function (IGF) or DGF. RESULTS: DGF observed in 241 patients (31.6%) was associated independently with expanded criteria donors, extended cold ischemia time, Karpinsky histological score, and prior dialysis duration both univariate and multivariate analysis. The incidence of acute rejection episodes was 18.1% among the DGF group versus 1.3% in the IGF group (P < .01). DGF significantly reduced both graft and patient survivals at 6, 12, 36, and 60 months. CONCLUSION: DGF was responsible for a longer hospital stay, worse early and long-term renal function, a higher incidence of acute rejection episodes as well as reduced graft and patient survivals.

Rectovaginal fistula is usually a challenging condition for surgeons, but a fistula between the rectum and the neovagina in male-to-female transsexual is even more difficult to treat as it is a rare complication occurring in a patient with modified anatomy of the perineum, with heavy psychological implications for the patient. Here, we report a case of recurrent recto-neovaginal fistula in a male-to-female transsexual successfully treated by perineal graciloplasty.

PURPOSE: Kidney retransplantation is the best treatment option for transplanted patients returning to dialysis. The aim of this study was to explore the effect of removal of a failed graft on the outcome of a subsequent transplant. METHODS: We identified 140 patients who underwent retransplantation at our institution. Retrospective comparison was performed between patients undergoing kidney retransplantation with (group A, n = 28) and without (group B, n = 112) preliminary nephrectomy. Graft and patient survival were calculated by the Kaplan-Meier method. RESULTS: After a mean follow-up of 64.5 months, patients survival was comparable between the two groups (group A = 68.6 vs. group B = 63.5 months; p = 0.6). Mean graft survival was 65.5 versus 56.0 months in group A and B, respectively (p = 0.14). Surgical complications after retransplantation were significantly higher in group A compared to group B (57.1 vs. 19.6 %; p = 0.0002). There was no significant difference between the two groups in the panel reactive antibody level at the time of retransplantation (group A = 20 % vs. group B = 32 %; p = 0.22). The acute rejection rate was 35.7 % in group A and 25 % in group B (p = 0.36). The risk of delayed graft function was not significantly increased in group A (p = 0.63). Finally, 2 years after retransplantation, patients who had not undergone nephrectomy had lower serum creatinine concentrations (1.3 vs. 1.7 mg/dl; p = 0.01) and higher estimated GFR (77.9 vs. 59.3 ml/min/1.73 m(2); p = 0.02). CONCLUSION: Our experience shows that there is no advantage in performing allograft nephrectomy before retransplantation, and that this procedure does not seem to significantly influence the survival of a subsequent graft.

Glucose-6-phosphate isomerase (GPI), also known as phosphoglucose isomerase, was initially identified as the second glycolytic enzyme that catalyzes the interconversion of glucose-6-phosphate to fructose-6-phosphate. Later studies demonstrated that GPI was the same as the autocrine motility factor (AMF), and that it mediates its biological effects through the interaction with its surface receptor (AMFR/gp78). In this study, we assessed the role of GPI/AMF as a prognostic factor for clear cell renal cell carcinoma (ccRCC) cancer-specific (CSS) and progression-free survival (PFS). In addition, we evaluated the expression and localization of GPI/AMF and AMFR, using tissue microarray-based immunohistochemistry (TMA-IHC), indirect immunofluorescence (IF), and confocal microscopy analysis.Primary renal tumor and nonneoplastic tissues were collected from 180 patients who underwent nephrectomy for ccRCC. TMA-IHC and IF staining showed an increased signal for both GPI and AMFR in cancer cells, and their colocalization on plasma membrane. Kaplan-Meier curves showed significant differences in CSS and PFS among groups of patients with high versus low GPI expression. In particular, patients with high tissue levels of GPI had a 5-year survival rate of 58.8%, as compared to 92.1% for subjects with low levels (P < 0.0001). Similar findings were observed for PFS (56.8% vs 93.3% at 5 years). At multivariate analysis, GPI was an independent adverse prognostic factor for CSS (HR = 1.26; P = 0.001), and PFS (HR = 1.16; P = 0.01).In conclusion, our data suggest that GPI could serve as a marker of ccRCC aggressiveness and a prognostic factor for CSS and PFS.

INTRODUCTION: Dual kidney transplantation (DKTx) to reduce the disparity between demand and supply of organs was evaluated in two Italian centers (Bari and Novara). MATERIALS AND METHODS: Between October 2000 and October 2011, we performed 97 DKT (26 ipsilateral/71 bilateral) following routine biopsy of all kidneys obtained from expanded criteria donors by Remuzzi-Karpinsky scores. The reference group was 379 single grafts from donors older than 60 years single kidney transplantation ([SKT] × > 60). RESULTS: Good postoperative renal function was observed in 56 DKTx (57.7%); whereas acute tubular necrosis requiring dialysis was observed in 41 (42.3%) patients. After a mean follow-up of 60 months, DKTx graft survivals were 96%, 93%, and 90% and patient survivals, 96%, 91%, and 91% at 1, 3, and 5 years, respectively. Complications in expanded criteria donor kidney transplantations included a high rate of cytomegalovirus (CMV) disease especially dual kidney cases. DKTx represented the only independent risk factor for CMV disease upon multivariate analysis (odds ratio [OR] 2.33, 95% confidence interval [CI] 1.28-4.2; P = .006). We did not observe any significant difference in graft or patient survival between DKTx and SKTx > 60 years. CONCLUSIONS: We observed good outcomes up to 5 years after transplantation in terms of graft and patient survival despite the use of inferior grafts. Comparing DKTx and SKT > 60, we noted that the mean Karpinski score for SKTx was significantly better than DKTx, although patient and graft survivals were similar. This trend confirms that the use of a biopsy to allocate expanded criteria donor kidneys may be too protective; therefore, the criteria to select DKTx require further refinement.

Protein analysis in biological fluids, such as urine, by means of mass spectrometry (MS) still suffers for insufficient standardization in protocols for sample collection, storage and preparation. In this work, the influence of these variables on healthy donors human urine protein profiling performed by matrix assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS) was studied. A screening of various urine sample pre-treatment procedures and different sample deposition approaches on the MALDI target was performed. The influence of urine samples storage time and temperature on spectral profiles was evaluated by means of principal component analysis (PCA). The whole optimized procedure was eventually applied to the MALDI-TOF-MS analysis of human urine samples taken from prostate cancer patients. The best results in terms of detected ions number and abundance in the MS spectra were obtained by using home-made microcolumns packed with hydrophilic-lipophilic balance (HLB) resin as sample pre-treatment method; this procedure was also less expensive and suitable for high throughput analyses. Afterwards, the spin coating approach for sample deposition on the MALDI target plate was optimized, obtaining homogenous and reproducible spots. Then, PCA indicated that low storage temperatures of acidified and centrifuged samples, together with short handling time, allowed to obtain reproducible profiles without artifacts contribution due to experimental conditions. Finally, interesting differences were found by comparing the MALDI-TOF-MS protein profiles of pooled urine samples of healthy donors and prostate cancer patients. The results showed that analytical and pre-analytical variables are crucial for the success of urine analysis, to obtain meaningful and reproducible data, even if the intra-patient variability is very difficult to avoid. It has been proven how pooled urine samples can be an interesting way to make easier the comparison between healthy and pathological samples and to individuate possible differences in the protein expression between the two sets of samples.

INTRODUCTION: The implantation of penile prostheses is an effective option for treating erectile dysfunction (ED), and nowadays it is used to treat those cases where pharmacological agents have not provided a useful result. AIMS: The primary aim of the present study was to verify the patient and their partner's satisfaction, in 80 patients who underwent AMS CX 700 prostheses implant in a single center, by the same surgeon, in the period between 2004 and 2008. METHODS: In the period between March 2004 and May 2008, 80 penile prostheses implantations have been performed. Any information regarding patients has been retrospectively collected consulting their case histories stored in our archive. Each patient was followed postoperatively, and surgical complications were recorded. MAIN OUTCOME MEASURE: All the patients entered in this study were contacted by phone by a single operator who asked for their consent to collect information regarding their operation, the use of the prostheses, and the couple satisfaction. Once the consent was obtained, a nine-point questionnaire was administered. RESULTS: Seventy-six patients (97%) affirmed to use penile prostheses frequently. Fifty-four patients (69%) and 70 partners (90%) affirmed that they never had problems with the use of the prosthesis and they considered themselves satisfied. Sixty-two patients (79%) answered that this therapeutic method has led to evident improvements in their sexual life. Sixty-two patients (79%) gave a score equal or major than seven and sixty-four partners (82%) gave a score equal or major than seven. All but two patients (97%) reported they would suggest this treatment to other people. CONCLUSIONS: Penile prosthetic surgery constitutes a valid therapeutic alternative, capable of modifying the prognosis and the course of ED. This consideration is emphasized by the high rate of patients and partner's satisfaction emerged in our series and in literature.

In this paper we studied the in vivo neoadjuvant Androgen Deprivation Therapy (ADT) effect on the expression of TGF-beta 1 and its receptor T beta-RII. Mechanisms of androgen dependence are critical to understanding prostate cancer progression to androgen independence associated with disease mortality, and TGF-beta is thought to support prostatic apoptosis as its expression coincides with androgen ablation in benign and cancer tissues. Increase of both mRNA and protein level were shown for the first time only in the patients who underwent neoadjuvant ADT for 1-month. This transient increase of TGF-beta expression after androgen ablation suggested cooperation of the pathways in prostate regression. Since no alteration was observed in the gene transcriptional activity, the molecular mechanism of this cooperation, probably act at the post-transcriptional level. TGF-beta 1 and T beta-RII specific signals were co-localized within the neoplastic prostate epithelium. our results suggests that the androgens deprivation by means of ADT for 1-month, involves a shift of the TGF-beta 1 mechanism in prostate cancer, suggesting that the TGF-beta 1 promotes prostate epithelial cell proliferation and inhibits apoptosis in a autocrine way. (C) 2011 Elsevier Ireland Ltd. All rights reserved.

BACKGROUND: Sarcosine is reported to be a differential metabolite that is greatly increased during prostate cancer (PCa) progression. In this study, we assessed the role of serum sarcosine as a biomarker for PCa, as well as any association between sarcosine levels and clinical-pathological parameters. METHODS: Sarcosine was measured by fluorometric assay in serum samples from 290 PCa patients and 312 patients with no evidence of malignancy (NEM), confirmed by 8-12 core prostate biopsies. Nonparametric statistical tests and receiver operating characteristics (ROC) analyses were performed to assess the diagnostic performance of sarcosine in different (prostate-specific antigen) PSA ranges. RESULTS: ROC analyses in subjects with PSA < 4 ng/ml showed a higher predictive value of sarcosine (AUC = 0.668) versus total PSA (AUC = 0.535) (P = 0.03), whereas for the other two PSA ranges (4-10 ng/ml and >10 ng/ml), percent ratio of free to total PSA (%fPSA) showed a predictive superiority over sarcosine. Moreover, in patients with a PSA < 4 ng/ml, the percentage of low/intermediate-grade cancers was positively associated with sarcosine levels (P = 0.005). The specificities for serum sarcosine, %fPSA, PSA, and the logistic regression model at 95% sensitivity were 24.4, 3.41, 2.22, and 28.4%, respectively. CONCLUSIONS: We provide evidence that serum sarcosine has a higher predictive value than tPSA and %fPSA in patients with PSA < 4 ng/ml. Moreover, sarcosine levels were significantly different in low grade versus high grade cancers in this subset of patients, suggesting that this marker may be a further tool not only for diagnosing PCa in normal PSA and abnormal DRE/TRUS patients but also for selecting candidates for non-aggressive therapies and active surveillance.

Aim: Sarcosine has been identified as a differential metabolite that is greatly increased during progression from normal tissue to prostate cancer and metastatic disease. In this study we assessed the role of serum sarcosine in metastatic castration-resistant prostate cancer (mCRPC) patients. Patients & methods: Data from 52 mCRPC patients treated with docetaxel-based chemotherapy were retrospectively analyzed. Receiver operating characteristic curves, and Kaplan-Meier and Cox multivariate analyses were performed. Results: Median sarcosine values were significantly higher in mCRPC versus non-mCRPC patients (0.81 vs 0.52 nmol/µl; p < 0.0001). A significant correlation resulted between serum sarcosine levels and the duration of hormone sensitivity (Spearman's correlation coefficient: -0.51; p = 0.001). At multivariate analysis sarcosine was an independent prognostic factor of outcome in terms of overall and progression-free survival. Conclusion: Serum sarcosine values were significantly increased in patients with metastatic disease. Moreover, this biomarker is a risk factor for progression and survival in chemotherapy-treated mCRPC patients.

Introduction & Objectives: High-throughput analysis of low-molecular-weight metabolites, represents a new tool for the global assessment of a cellular state, taking into account genetic regulation, altered kinetic activity of enzymes, and changes in metabolic reactions and regulation. Recently, sarcosine, an N-methyl derivative of glycine, was identified as a differential metabolite highly increased during prostate cancer (PCa) progression. In the present study we assessed the utility of sarcosine detected in serum as a biomarker for PCa and reported the association between the sarcosine levels and clinical-pathological parameters. Materials & Methods: In prospective fashion, sarcosine was measured in serum samples from subjects 289 PCa patients and 312 patients with no evidence of malignancy (NEM), confirmed by 8–12 core prostate biopsies. Sarcosine was measured using the Sarcosine Assay Kit (Biovision, Mountain View, CA, USA) following the manufacturer’s instructions. Nonparametric statistical tests and receiver operating characteristics (ROC) analyses were performed to assess the diagnostic performance. Results: According to A. Sreekumar et al. study, we initially restricted the analysis to patients with PSA values in the grey zone of 2-10 ng/ml, but we didn’t find a better diagnostic performance of sarcosine (AUC=0.57; 95% CI: 0.52, 0,62) vs total PSA (AUC=0.56; 95% CI: 0.51, 0,61) (p=0.7) and vs % fPSA. (AUC=0.68; 95% CI: 0.63, 0,73) (p=0.004). After we investigated the performance of sarcosine in other range of PSA (PSA<4 ng/ml; 410 ng/ml). ROC analysis on subjects with PSA<4 mg/l showed a higher predictive value of sarcosine vs total PSA (sarcosine AUC= 0.668; 95% CI: 0.58 to 0,74 vs total PSA AUC=0,53; 95% CI: 0.45 to 0,62) (p=0.039). ROC analyses for the other two ranges of PSA, showed the predictive superiority of %PSA vs sarcosine. Sarcosine values were not associated with tumour stage (pT2 vs pT3) or grade (Gleason score <7 vs ≥7). Conclusions: We reported the first independent study to validate the role of serum sarcosine in the diagnosis of prostate cancer. We provided evidence that serum sarcosine had a higher predictive value than tPSA and % fPSA in patients with PSA<4 ng/ml. Moreover serum sarcosine was not associated with tumor stage and grade, weakening its possible role in predicting cancer aggressiveness, as initially postulated

Purpose: Deviceless hand-assisted laparoscopic living donor nephrectomy is an alternative surgical technique that relies on the classic laparoscopic approach, supported by insertion of the surgeon's hand during kidney recovery without the need to use any device because of the sealing effect of the particular wall incision. Patients and Methods: From 2006 to 2008, deviceless hand-assisted laparoscopic living donor nephrectomy was performed in 25 patients (M/F = 7/18; mean age = 53 years; range = 30-68). One right nephrectomy was performed. We made a lateral paramedian incision. No sealing device is required in our technique because the pneumoperitoneum is maintained by the sealing effect of two complexes: the peritoneum/deep rectus abdominis muscle fascia and muscle itself/lateral edge of the double fascial incision. These structures clench around the surgeon's wrist, preventing leakage of CO(2). After dissection, the kidney is removed through the hand port without an endobag. Results: Mean surgical time was 105 minutes (range = 60-150), estimated blood loss was 50 to 200 mL, and mean warm ischemia time was 3.5 minutes (range = 2-11). Mean hospital stay was 4 days (range = 3-6). One uncontrollable hemorrhage due to a renal vein lesion required conversion to open surgery. As to graft function, recipient serum creatinine on day 7 ranged from 0.8 to 2.6 mg/dL. Conclusions: The ability to better control bleeding by manual compression, as well as the advantages related to decreased donor morbidity, shorter hospital stay, cost saving, and excellent graft function, make this deviceless technique a good option for kidney recovery.